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A basic study for mitochondria-targeting liposome vector using human mitochondrial fusiogenic protein.

Research Project

Project/Area Number 14570129
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionJichi Medical University

Principal Investigator

ENDO Hitoshi  Jichi Medical School, Department of Biochemistry, Associate Professor, 医学部, 助教授 (50221817)

Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordsmitochondria / liposome / gene therapy / proteoliposome / membrane fusion / mitochondrial morphogenesis / mitochondrial membarne / GTP binding protein
Research Abstract

The mitochondria are organelle in the cell and have the proper DNA different from the nuclear genome. The development of the new way of introducing a material into the mitochondria, which is different from the usual gene therapy to the nuclear target, is necessary for the fundamental treatment of the mitochondrial disease based on the mitochondrial DNA. In this research, it aims at the fundamental development of new liposome vector that peculiarly targets the mitochondria, using the mitochondrial fusiogenc factor as an effective component. Such a vector will make it possible that not only normal mitochondrial DNA but also the drug adjusting the mitochondrial function and/or the exogenous ribozyme regulating the mitochondrial transcripts are introduced into the mitochondria. The development of such a vector would become applied for a new drug delivery system for many diseases with dysfunction of the mitochondria in the future.
We identified a mitochondrial fusiogenic protein, a human Fzo homolog, and analyzed the domain of the protein necessary for membrane fusiogenic activity. We also produced the recombinant protein of the domain, reconstituted the proteoliposome using the protein, and proved the membrane fusiogenic activity of the liposome in vitro. On the other hand, we examined the OPA1 protein which has the mitochondrial fusiogenic activity, and showed the differential sublocalization of OPA1 isoform in the human cell. This factor is one of the assistant factors of the mitochondrial fusiogenic device, which will be important for improvement for the efficiency of the liposome vector. Next step requires an examination whether the mitochondrial DNA-embedded liposome, introduced in the cell by microinjection, actually targets the mitochondria in vivo. This research is the first step to establish the fundamental technology of the gene therapy of mitochondrial diseases.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (36 results)

All 2005 2004 2003 2002 Other

All Journal Article (22 results) Publications (14 results)

  • [Journal Article] Activation of Pre-mRNA Splicing by Human RNPS1 Is Regulated by CK2 Phosphorylation.2005

    • Author(s)
      Trembley, J.H.
    • Journal Title

      Mol.Cell.Biol. 25

      Pages: 1446-1457

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Activation of Pre-mRNA Splicing by Human RNPS1 Is Regulated by CK2 Phosphorylation.2005

    • Author(s)
      Trembley, J.H., Tatsumi, S., Sakashita, E., Loyer, P., Slaughter, C.A., Suzuki, H., Endo, H., Kidd, V.J., Mayeda, A.
    • Journal Title

      Mol.Cell.Biol. 25

      Pages: 1446-1457

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Damaged DNA-binding protein 2 accelerates UV- damaged DNA repair in human corneal endothelium.2004

    • Author(s)
      Inoki, T.
    • Journal Title

      Exp.Eye Res. 79(3)

      Pages: 367-376

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Establishment of Cre/LoxP recombination system in transgenic rats.2004

    • Author(s)
      Sato, Y.
    • Journal Title

      Biochem.Biophys.Res.Commun. 319

      Pages: 1197-1202

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Human RNPS1 and Its associated factors : a versatile alternative pre-mRNA splicing regulator in vivo.2004

    • Author(s)
      Sakashita, E.
    • Journal Title

      Mol.Cell.Biol. 24

      Pages: 1174-1187

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Human DDB2 splicing variants are dominant negative inhibitors of UV-damaged DNA repair.2004

    • Author(s)
      Inoki, T.
    • Journal Title

      Biochem.Biophys.Res.Commun. 314

      Pages: 1036-1043

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Human DDB2 splicing variants are dominant negative inhibitors of UV-damaged DNA repair.2004

    • Author(s)
      Inoki, T., Yamagami, S., Inoki, Y., Tsuru, T., Hamamoto, T., Kagawa, Y., Mori, T., Endo, H.
    • Journal Title

      Biochem.Biophys.Res.Commun. 314

      Pages: 1036-1043

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Human RNPS1 and Its associated factors : a versatile alternative pre-mRNA splicing regulator in vivo.2004

    • Author(s)
      Sakashita, E., Tatsumi, S., Werner, D., Endo, H., Mayeda, A.
    • Journal Title

      Mol.Cell.Biol. 24

      Pages: 1174-1187

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Establishment of Cre/LoxP recombination system in transgenic rats.2004

    • Author(s)
      Sato, Y., Endo, H., Ajiki, T., Hakamata, Y., Okada, T., Murakami, T., Kobayashi, E.
    • Journal Title

      Biochem.Biophys.Res.Commun. 319

      Pages: 1197-1202

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Damaged DNA-binding protein 2 accelerates UV-damaged DNA repair in human corneal endothelium.2004

    • Author(s)
      Inoki, T., Endo, H., Inoki, Y., Hamamoto, T., Tsuru, T., Mori, T., Miyata, K., Amano, S., Yamagami, S.
    • Journal Title

      Exp.Eye Res. 79(3)

      Pages: 367-376

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A member of Forkhead transcription factor FKHRL1 is a downstream effector of STI571-induced cell cycle arrest in BCR-ABL expressing cells2003

    • Author(s)
      Komatsu, N., Watanabe, T., Uchida, M., Mori, M., Kirito, K., Kikuchi, S., Liu, Q., Tauchi, T., Miyazawa, K., Endo, H., Nagai, T., Ozawa, K.
    • Journal Title

      J.Biol.Chem. 278

      Pages: 6411-6419

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Differential sublocalization of Dynamin-related protein OPA1 isoforms in mitochondria.2003

    • Author(s)
      Satoh, M., Hamamoto, T., Seo, N., Kagawa, Y., Endo, H.
    • Journal Title

      Biochem.Biophys.Res.Commun. 300

      Pages: 482-493

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Stage-specific regulatory element of mouse Sry gene.2003

    • Author(s)
      Yokouchi, K., Ito, M., Nishino, K., Yamanouchi, K., Naito, K., Suzawa, M., Kato, S., Hakamata, Y., Endo, H., Tojo H.
    • Journal Title

      Mol.Reprod.Dev. 64

      Pages: 389-396

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Defective sorting to secretory vesicles in trans-Golgi network is partly responsible for protein C deficiency. Molecular mechanisms of impaired secretion of abnormal protein C R169W, R352W, and G376D.2003

    • Author(s)
      Naito, M., Mimuro, J., Endo, H., Madoiwa, S., Ogata, K.-I., Kikuchi, J., Sugo, T., Yasu, T., Kariya, Y., Hoshino, Y., Sakata, Y.
    • Journal Title

      Circ.Res. 92

      Pages: 865-872

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A vertebrate RNA-binding protein Fox-1 regulates tissue-specific splicing via the pentanucleotide GCAUG.2003

    • Author(s)
      Jin, Y., Suzuki, H., Maegawa, S., Endo, H., Sugano, S., Hashimoto, K., Yasuda, K., Inoue, K.
    • Journal Title

      EMBO J. 22

      Pages: 905-912

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Polymorphism, heteroplasmy, mitochondrial fusion and diabetes.2003

    • Author(s)
      Sato, A., Endo, H., Umetsu, K., Sone, H., Yanagisawa, Saigusa, A., Aita, S., Kagawa, Y.
    • Journal Title

      Bioscience Rep. 23

      Pages: 313-337

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Polymorphism, heteroplasmy, mitochondrial fusion and diabetes.2003

    • Author(s)
      Sato, A.
    • Journal Title

      Bioscience Rep. 23

      Pages: 313-337

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Muscle-specific exonic splicing silencer for exon exclusion in human ATP synthase gamma-subunit pre-mRNA.2002

    • Author(s)
      Hayakawa, M., Sakashita, E., Ueno, E., Tominaga, S., Hamamoto, T., Kagawa, Y., Endo, H.
    • Journal Title

      J.Biol.Chem. 277

      Pages: 6974-6984

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Isoliquiritigenin suppresses pulmonary metastasis of mouse renal cell carcinoma.2002

    • Author(s)
      Yamazaki, S., Morita, T., Endo, H., Hamamoto, T., Baba, M., Joichi, Y., Kaneko, S., Okada, Y., Okuyama, T., Nishino, H., Tokue, A.
    • Journal Title

      Cancer Lett. 183

      Pages: 23-30

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Apaf-1 is a mediator of E2F-1-induced apoptosis.2002

    • Author(s)
      Furukawa, Y., Nishimura, N., Furukawa, Y., Satoh, M., Endo, H., Iwase, S., Yamada, H., Matsuda, M., Kano, Y., Nakamura, M.
    • Journal Title

      J.Biol.Chem. 277

      Pages: 39760-39768

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] cDNA cloning and characterization of Drb1, a new member of RRM-type neural RNA-binding protein.2002

    • Author(s)
      Tamada, H., Sakashita, E., Shimazaki, K., Ueno, E., Hamamoto, T., Kagawa, Y., Endo, H.
    • Journal Title

      Biochem.Biophys.Res.Commun. 297

      Pages: 96-104

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] In vitro Cre-loxP system in cells from developing gonads : Investigation of the Sry promoter.2002

    • Author(s)
      Ito, M., Yokouchi, K., Naito, K., Endo, H., Hakamata, Y., Miyazaki, J.-I., Tojo H.
    • Journal Title

      Dev.Growth Differ. 44

      Pages: 549-557

    • NAID

      50000720752

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Inoki, T.: "Human DDB2 splicing variants are dominant negative inhibitors of UV-damaged DNA repair."Biochem.Biophys.Res.Commun.. 314. 1036-1043 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sakashita, E.: "Human RNPS1 and Its associated factors : a versatile alternative pre-mRNA splicing regulator in vivo."Mol.Cell.Biol.. 24. 1174-1187 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Naito, M.: "Defective sorting to secretory vesicles in trans-Golgi network is partly responsible for protein C deficiency."Circ.Res.. 92. 865-872 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yokouchi, K.: "Stage-specific regulatory element of mouse Sry gene."Mol.Reprod.Dev.. 64. 389-396 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Jin, Y.: "A vertebrate RNA-binding protein Fox-1 regulates tissue-specific splicing via the pentanucleotide GCAUG."EMBO J.. 22. 905-912 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Satoh, M.: "Differential sublocalization of Dynamin-related protein OPA1 isoforms in mitochondria."Biochem.Biophys.Res.Commun.. 300. 482-493 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 遠藤仁司: "分子生物学イラストレイテッド 改訂第2版"田村隆明、山本 雅 編集、羊土社. 380 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Jin, Y.: "A vertebrate RNA-binding protein Fox-1 regulates tissue-specific splicing via the pentanucleotide GCAUG"EMBO J. 22. 905-912 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Satoh, M.: "Differential sublocalization of the dynamin-related protein DPA1 isoforms in mitochondria"Biochem.Biophys.Res.Commun.. 300. 482-493 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tamada, H.: "cDNA cloning and characterization of Drb1, a new member of RRM-type neural RNA-binding protein"Biochem.Biophys.Res.Commun.. 297. 96-104 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Furukawa, Y.: "Apaf-1 is a mediator of E2F-1-induced apoptosis"J.Biol.Chem.. 277. 39760-39768 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hayakawa, M.: "Muscle-specific exonic splicing silencer for exon exclusion in human ATP synthase γ-subunit pre-mRNA"J.Biol.Chem.. 277. 6974-6984 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kirito, K.: "TPO regulates Bcl-xL gene expression through Stat5 and phosphatidylinositol-3-kinase activation pathways"J.Biol.Chem.. 277. 8329-8337 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 遠藤 仁司: "分子生物学 イラストレイテッド 改訂第2版"田村隆明,山本雅編 羊士社. 380 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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